TR&D Project 3: Photoacoustic Detection of Metal Fluxes at the Tissue Level

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• 批准号: 10494062
• 负责人: Hao F Zhang
• 金额: $ 18.44万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10494062
• 关键词: 3-Dimensional; Adopted; Animal Model; Animals; Biological; Biological Process; Biological Sciences; Brain; Bypass; Cells; Coupling; Cryopreservation; Cryopreserved Tissue; Deposition; Detection; Development; Ensure; Extinction (Psychology); Fluorescence; Fluorescence Microscopy; Fluorescent Probes; Future; Generations; Goals; Hemoglobin; Image; Investigation; Ions; Kidney; Label; Larva; Lasers; Measurement; Measures; Metals; Microfluidics; Microscopic; Microscopy; Modality; Modernization; Molecular; Molecular Probes; Mus; Optics; Organ; Pathologic Processes; Pathway interactions; Physiological Processes; Preparation; Process; Research; Research Personnel; Resolution; Resources; Roentgen Rays; Sampling; Slice; System; Technology; Testing; Thick; Tissue imaging; Tissues; Ultrasonic wave; Zebrafish; absorption; base; contrast imaging; design; detection method; detection sensitivity; detector; fluorescence imaging; hemodynamics; imaging capabilities; imaging platform; improved; iron metabolism; microscopic imaging; multi-photon; nanoimprinting; novel; optical imaging; pressure; quantum; response; second harmonic; technology research and development; tool; ultrasound; vibration; waveguide

PROJECT SUMMARY – TR&D PROJECT 3 Photoacoustic Detection of Metal Fluxes at the Tissue Level Modern optical microscopic modalities offer the following optical contrasts: optical scattering, autofluorescence (intrinsic fluorescence), molecular probes (extrinsic fluorescence), and nonlinear optical effects. One key contrast, optical absorption, is inaccessible by established microscopic modalities. As a result, bioelement investigation in biological tissue mainly rely on various fluorescence probes. A lasting challenge in designing fluorescence probes is to overcome low quantum yield, where major optical energy deposited to the probes is dissipated via a non-radiative pathway as heat instead of as fluorescent emissions. Measuring nonradiative thermal generation or optical absorption could offer a new way to conduct bioelement imaging and bypass the quantum yield challenge. Imaging optical absorption quantifies ionic concentrations with high accuracy when the molar extinction coefficient is known. Imaging optical absorption permits direct quantitation of certain highly-optically absorbing ions (i.e. Fe in hemoglobin) and will stimulate the development of a new class of molecular probes that focus on high extinction coefficients only, for which the struggle to achieve high fluorescent quantum yield becomes much less critical. In this Technology Research and Development (TR&D) project we will develop a new optical absorption microscopy modality, referred to as optical Micro-Ring Resonator-Based Photoacoustic Microscopy or MRR- PAM, which measures optical absorption using ultrasound. MRR-PAM detects ultrasound waves induced by laser energy absorption and, consequently, heat generation and thermoelastic vibration. Compared with existing photoacoustic microscopy, MRR-PAM improves the ultrasound detection bandwidth and axial resolution by 10-fold and detection sensitivity by 100-fold. MRR-PAM provides a unique tool to enable tissue imaging in all the DBP themes, such as the strongly scattering brain slices, thick tissue slice or whole mouse kidney, whole zebrafish and zebrafish larvae. It will provide a new tool to quantify iron metabolism. MRR-PAM extends the imaging capabilities developed in other TR&D projects to quantify bioelement distributions and fluxes in both fixed and living tissue slices. It offers the possibility to image whole organs and, potentially, living animals. The unique MRR developed in this TR&D project can be broadly disseminated and will likely impact several other biomedical fields beyond bioelement research.

项目摘要 – TR&D 项目 3 组织水平金属通量的光声检测 现代光学显微模式提供以下光学对比：光学散射、自发荧光 （内在荧光）、分子探针（外在荧光）和非线性光学效应。 相比之下，光学吸收是通过现有的微观模式无法实现的。 生物组织的研究主要依赖于各种荧光探针的设计是一个持久的挑战。 荧光探针的目的是克服低量子产率，其中沉积到探针上的主要光能是 通过非辐射途径以热量而不是荧光发射的形式消散。 测量非辐射热产生或光吸收可以提供一种进行生物元素的新方法 成像并绕过量子产率挑战。成像光学吸收量化离子浓度。 当摩尔消光系数已知时，可以实现高精度成像。 某些高光学吸收离子（即血红蛋白中的 Fe）的定量，并将刺激发育 一种仅关注高消光系数的新型分子探针，为此，我们需要努力 实现高荧光量子产率变得不再那么重要。 在这个技术研发（TR&D）项目中，我们将开发一种新的光学吸收 显微镜模式，称为基于光学微环谐振器的光声显微镜或 MRR- PAM，使用超声波测量光吸收，检测由超声波引起的超声波。 与激光能量吸收以及由此产生的热量和热弹性振动相比。 与现有光声显微镜相比，MRR-PAM 提高了超声检测带宽和轴向 MRR-PAM 的分辨率提高了 10 倍，检测灵敏度提高了 100 倍，为组织提供了独特的工具。 所有 DBP 主题的成像，例如强散射脑切片、厚组织切片或整个小鼠 肾脏、整个斑马鱼和斑马鱼幼虫它将提供一种量化铁代谢的新工具。 扩展了其他 TR&D 项目中开发的成像功能，以量化生物元素分布和 它提供了对整个器官甚至活体器官进行成像的可能性。 该 TR&D 项目中开发的独特 MRR 可以广泛传播，并可能会产生影响。 生物元素研究之外的其他几个生物医学领域。